DE102017012306B3 - Ion injection into an electrostatic trap - Google Patents

Abstract

A method for injecting ions into an orbital-type electrostatic trap (70), comprising: applying an ejection potential (103) to an ion storage device (50) to cause ejection of ions stored in the ion storage device (50) toward the orbital-type electrostatic trap ( 70), andapplying one or more injection potentials (105, 106, 115, 116) to an electrode (72) associated with the electrostatic trap (70) to cause the capture of the ions ejected from the ion storage device (50) by the causing electrostatic traps (70) to revolve around a central electrode (72); andwherein the steps of applying the ejection potential (103) and applying one or more injection potentials (105, 106, 115, 116) each begin at different times, the difference (110, 120) in times being at desired values of mass-to-charge ratios of ions to be trapped by the electrostatic trap (70), and wherein an RF potential is generated at a predetermined frequency and the difference between respective start times of the steps of applying the ejection potential (103) and applying the one or more injection potentials (105 , 106, 115, 116) is measured using the predetermined frequency of the HF potential.

Description

Technical field of the invention

The invention relates to a method for injecting ions into an electrostatic trap composed of an ion storage device and an associated mass spectrometer.

Background of the Invention

The use of electrostatic traps as mass analyzers such as the orbital trap mass analyzer (marketed under the name Orbitrap(TM)) has provided high resolution mass spectra with a high dynamic range. This type of mass spectrometry, particularly using the orbital trap mass analyzer, is increasingly used to detect small organic molecules as well as large intact proteins and native protein complexes.

The intrinsic ability of this type of mass analyzer to trap molecular species at the extremes of broader mass/charge (m/z) ratio ranges may depend on the quality of ion injection into the electrostatic trap. To aid in understanding the injection process it is useful to consider the operation of an existing mass analyzer of this type.

U.S. 2004 108 450 A1 refers to a mass spectrometer that includes an ion source that produces nebulized ions that enter an ion cooler via an ion source block, where ions within a window of m/z of interest are extracted via a quadrupole mass filter and directed to a linear trap . The ions are trapped in a potential well in the linear trap and are focused at the bottom of the potential well near an exit segment and directed out of the linear trap into an electrostatic ion trap where they are detected by a secondary electron multiplier. WO 2012 116 765 A1 relates to an electrostatic ion trap for mass analysis with electrode arrays, which may be planar arrays formed by parallel stripe electrodes or by concentric, circular or part-circular electrically conductive rings, and which are supplied with essentially the same voltage pattern, the distribution of the electric potential is such that the ions are reflected isochronously in a direction of flight, thereby undergoing a periodic, oscillating motion in space, focused substantially midway between the arrays.

U.S. 2007 158 545 A1 refers to an unbalanced radiofrequency (RF) field that creates a retarding barrier near the exit aperture of a multipole ion guide, in combination with an extractive DC field, such that the barrier allows m/z-dependent cutting of ion sampling.

With reference to 1 1 is a schematic of a prior art mass spectrometer utilizing an orbital trap mass analyzer. This mass spectrometer is marketed under the name Exactive Plus(TM) by Thermo Fisher Scientific. This mass spectrometer comprises: an atmospheric pressure ionization ion source 10, source injection optics 20, a flatapole curved ion guide 30, a transfer multipole ion optics device 40, a curved linear trap (CLT or C-trap) 50, a Z-lens 60, an orbital trap mass analyzer 70, a Higher Energy Collision Dissociation (HCD) collision cell 80, and a collector 90. The source injection optics 20 comprises: a capillary 21; an S lens 22; an S-lens exit lens 23; an injection flatapole ion optics device 24; and an inter flatapole lens 25. Also provided are: a flatapole exit lens 35, a hemilens 36, a C-trap entry lens 53, and a C-trap exit lens 55.

As is known, the orbital trap mass analyzer 70 is axisymmetric and comprises a spindle-shaped central electrode (CE) 72 surrounded by a bell-shaped pair of outer electrodes 75 . Electric fields within the mass analyzer are used to trap and confine ions therein such that trapped ions undergo repeated oscillations in an axial direction of the analyzer as they orbit around the central electrode. A deflector electrode 65 is provided adjacent the entrance aperture to the orbital trap mass analyzer 70 to deflect ions into the entrance. Ions are injected at high energies (typically 1-2 keV per charge) from the CLT 50 into the orbital trap mass analyzer 70 to achieve dynamic trapping. When injection takes place over hundreds of microseconds at such energies, the process can extend over hundreds of ion reflections. Without any collisional cooling outside of the electrostatic trap, ion stability can be compromised. To enable efficient ion trapping, a time propagation of an ion packet in the vicinity of the injection slit should be shorter than half a period of axial ion oscillation in the electrostatic trap. Therefore, a short injection time is used, which places high demands on ion trapping. Although it's the masses Although the analyzer in this example is an orbital trap type analyzer, similar considerations apply to ion injection into other electrostatic traps, which often have stringent ion injection and trapping requirements.

in the in 1 In the illustrated example, injecting into the orbital trap mass analyzer 70 involves the C-trap 50. Ions are emitted from the C-trap 50 perpendicular to the direction in which they enter the C-trap 50 from the transfer multipole ion optics device 40 for analysis. pushed out. This is accomplished by ramping down an RF potential applied to the rods of the C-Trap and applying extraction voltage pulses to the electrodes. The initial curvature of the C-Trap 50 and subsequent lenses, e.g. B. the Z-lens 60, causes convergence of the ion beam at the entrance to the orbital trap mass analyzer 70. The Z-lens 60 also has differential pumping slits (which electrostatically deflect the ions from the gas stream and thereby prevent gas from being carried over into the analyzer) and thus causes a spatial focusing of the ion beam in the entrance of the orbital trap mass analyzer 70.

The rapid pulsing of ions from the C-trap 50 causes ions of any mass/charge ratio to arrive at the entrance of the orbital trap mass analyzer 70 as short packets only a few millimeters long. For ions of any mass/charge species, this corresponds to a propagation of flight times of only a few hundred nanoseconds for mass/charge ratios of a few hundred daltons per charge (1 dalton ≈ 1.66×10 ^-27 kg). Such time periods are substantially shorter than one-half period of ion axial oscillation in the electrostatic trap 70. When ions are injected into the orbital trap mass analyzer 70 at a position offset from its equator, these packets begin coherent axial oscillations without requiring an additional excitation cycle .

Injection may also be based on dynamic waveforms applied to deflector electrode 65 and CE 72 during an injection event. Collectively, these can be referred to as CE injection waveforms. The ionic species entering the analyzer during an injection event are subjected to a dynamic electric field in the capture region (between the CE 72 and the outer electrodes 75) and simultaneously orbit around the CE 72 during several initial axial periods of decreasing radius. This is the process known as dynamic compression is known. After injection, the potential applied to the CE 72 is dynamically varied, e.g. set more negative for trapping positive ions and more positive for trapping negative ions. The dynamic potential at the CE decreases the radial position of the ions in the trapping region during an injection event, leading to the trapping and subsequent detection of ions in the electrostatic trap.

A detailed discussion of this injection is also given in the international patent publication WO 2002 078 046 A2 provided and the contents of that document are incorporated herein by reference. for the inside 1 The mass spectrometer shown can routinely detect ions with an m/z ratio between 50 Thomson (Th corresponds to Dalton per elementary electric charge ≈ 1.036426× ^-28 kg·C ^-1 ) and 6000 Th. An improvement (and if possible optimization) in the range of m/z ratios that can be easily detected is desirable. Achieving such improvements, however, remains a challenge.

Summary of the Invention

Against this background a method for injecting ions into an electrostatic trap according to claim 1 and a mass spectrometer as defined in claim 23 is provided. Further features of the invention are detailed in the appended claims. The mass spectrometer can be used for mass analysis of ions trapped by the ion injection method in the electrostatic trap. An injection event involves two main parts: (a) applying an ejection potential to an ion storage device; and (b) applying one or more injection potentials to an electrode, which may be connected to an electrostatic trap (the electrostatic trap being an orbital trap-type trap). The ejection potential causes ions stored in the ion storage device to be ejected toward the electrostatic trap. The one or more ejection potentials cause the ions stored in the ion storage device to be ejected toward the electrostatic trap. In particular, synchronous injection potentials of different amplitudes can be applied simultaneously to the multiple electrodes associated with the electrostatic trap (e.g., a deflector and a center electrode). The ion storage device is suitably a linear ion trap and preferably a curved linear trap (referred to as a CLT or C-trap), particularly when an electrostatic trap of the orbital trap type is used.

Normally (a) and (b) have been started at the same time so far. Advantageously, at of the present invention (a) and (b) started at different times. The start times (or at least the difference between the start times in terms of direction and/or magnitude) are conveniently selected based on desired values of mass/charge ratios of ions to be trapped by the electrostatic trap (covered by one or more mass/charge ratio ranges can). In other words, to capture ions comprising those with a specific range of mass-to-charge ratios: either (a) can be launched before (b); or (b) can be launched before (a), and the choice between these two options depends on the specific range of mass-to-charge ratios. In another sense, the length of time between the start of (a) and the start of (b) may depend on the specific range of mass/charge ratios.

Using this technique, detection of ions with m/z ratios as low as 35 Th or as high as 20,000 Th (or higher) is possible; the range is thus much broader than the previous mode of operation, with improvements being made at both ends of the range. In addition, the m/z range of the mass spectrometer can advantageously be tuned for optimized ion detection. In this way, the ratio of the highest and lower m/z ratios within a spectrum can be as high as 40:1 and possibly even more. For example, a mass spectrum can be generated based on several "micro-scans" in the electrostatic trap, i. H. each of multiple ion injections into the electrostatic trap, made with different delay times between the ejection and injection potentials to achieve a higher range of m/z ratios. In other words, each scan is based on a different delay time and provides a mass spectrum of ions with a different m/z ratio range. A sum of such spectra provides a "composite" mass spectrum that has a higher range of m/z ratios than any single scan.

It has been found that if the desired range of mass/charge ratios of ions to be trapped by the electrostatic trap covers a range lower than a threshold mass/charge ratio (e.g. ca. 100 Thomson), (b ) should conveniently start before (a). The duration (magnitude) of this time difference may be at least that of an induction (settling) period associated with one or more injection potentials. The transient period can be about 1 µs, so (b) can start about 3 µs before (a). (b) can preferably start before (a) with a time difference of between 1 μs and 5 μs, 2 μs and 4 μs or approx. 3 μs.

On the other hand, if the desired range of mass-to-charge ratios of ions to be trapped by the electrostatic trap covers a range higher than a limit mass-to-charge ratio (e.g. about 8000 Thomson), then (a) should conveniently precede ( b) start. That is, the start of applying the one or more injection potentials is delayed relative to the start of applying the ejection potential. The duration of this time difference may be based on one or more of the following: a time period associated with the ejection potential; a time period associated with the one or more injection potentials; and a period of time associated with a time of flight for ions between the ion storage device and the electrostatic trap, in particular a time of flight for ions having a mass/charge ratio of at least the threshold mass/charge ratio. In particular, the time difference may be greater than the flight time for ions between the ion storage device and the electrostatic trap, but less than the sum of the flight time for ions between the ion storage device and the electrostatic trap (typically at least 15 µs for ions of about m/z 8,000 and higher) and the discharge time constant associated with the one or more injection potentials (e.g., about 10 µs). Therefore, in practice, a time difference of 15 to 25 µs, e.g. B. about 20 microseconds, are used. However, to trap the ions with the highest m/z value, e.g. B. time differences of 25 to 50 microseconds, longer delay times from (b) to (a) can be used.

If it is e.g. For example, when the electrostatic trap is an orbital trap type, it comprises a central electrode and a coaxial outer electrode. The coaxial outer electrode typically includes a pair of bell-shaped outer electrodes. Then the step of applying one or more injection potentials may include applying a trapping injection potential to the central electrode and/or the deflector. This may be a potential ramping down from a first injection potential level to a second, lower injection potential level. The second potential level can be a zero potential. For positive ion trapping, the trapping injection potential to the central electrode is preferably a potential dropped from a first negative potential level to a lower (ie, even more negative) potential level. So e.g. B. are the first potential level in the range of -3.2 kV to -3.7 kV and the second lower potential level at about 5kV. To my scavenging negative ions would reverse these polarities (i.e. positive potentials would be applied to the center electrode). The second potential level is preferably the final potential applied to the central electrode: ie the potential applied to the electrode during the detection of the ions in the electrostatic trap after the injection process. The duration of the potential ramp at the middle electrode from the first to the second potential level can be in the range from 5 µs to 200 µs, e.g. B. between 5 microseconds and 100 microseconds, but preferably 5 microseconds to 50 microseconds.

The ejection potential can be applied by decreasing a magnitude of a potential applied to an electrode of the ion storage device so that the ions stored in the ion storage device are ejected to the electrostatic trap. Reducing a magnitude of a potential applied to an electrode of the ion storage device suitably comprises turning off the potential, e.g. an RF potential applied to one or more electrodes of the ion storage device, e.g. B. an HF potential connected to multi-pole stick electrodes. The ejection potential may alternatively or preferably additionally be applied by applying an extraction potential to one or electrodes of the ion storage device, preferably in the form of one or more DC potentials applied to one or more electrodes. In one embodiment, DC potentials of opposite polarity can be applied to at least two electrodes of the ion storage device, causing the ions in the ion storage device to be pushed and pulled to eject them from the device. The duration of the ejection potential applied to the ion storage device may range from 5 µs to 40 µs, preferably from 10 µs to 20 µs.

The one or more injection potentials may include a deflecting injection potential applied to an ion deflector between the ion storage device and the electrostatic trap. This can cause the ions to move towards (and/or be focused onto an entrance aperture of) the electrostatic trap. Additionally or alternatively, the one or more injection potentials may comprise a trapping injection potential applied to an electrode of the electrostatic trap.

In embodiments where the electrostatic trap is an orbital trap type electrostatic trap, the trapping injection potential may be applied to a center electrode of the electrostatic trap around which the trapped ions orbit. The application of the capture injection potential and the distracting injection potential can begin simultaneously. This is convenient for the sake of simplicity. If they are not started simultaneously, the time difference relates to the application of the ejection potential to the capture injection potential and deflection injection potential, whichever starts first.

character list

• 1 ein bekanntes Massenspektrometer schematisch darstellt, bei dem ein Orbitalfallen-Massenanalysator zur Anwendung kommt;
• 2a Signalwellenformen für Injektions- und Ausstoßpotenziale zeigt, die an Teile des Massenspektrometers aus 1 nach einer Ausführungsform angelegt werden;
• 2b Signalwellenformen für Injektions- und Ausstoßpotenziale zeigt, die an Teile des Massenspektrometers aus 1 nach einer anderen Ausführungsform angelegt werden;
• 3 ein schematisches Blockdiagramm eines Steuerungssystems nach einer Ausführungsform zeigt;
• 4 beispielhafte Massenspektren für lonenspezies mit einem niedrigen Masse-/Ladungsverhältnisbereich zeigt, wobei (a) ein bestehender Ansatz verwendet wird und (b) eine Ausführungsform zur Anwendung kommt;
• 5 erste beispielhafte Massenspektren für lonenspezies mit einem hohen Masse-/Ladungsverhältnisbereich zeigt, wobei (a) ein bestehender Ansatz verwendet wird und (b) eine Ausführungsform nach einem ersten Ansatz zur Anwendung kommt;
• 6 zweite beispielhafte Massenspektren für lonenspezies mit einem hohen Masse-/Ladungsverhältnisbereich zeigt, wobei (a) ein bestehender Ansatz verwendet wird und (b) eine Ausführungsform nach einem zweiten Ansatz zur Anwendung kommt.

The invention can be put into practice in many ways and a preferred embodiment will now be described, by way of example only, with reference to the accompanying drawings, in which:

• 1 schematically illustrates a known mass spectrometer using an orbital trap mass analyzer;
• 2a Shows signal waveforms for injection and ejection potentials coming out of parts of the mass spectrometer 1 according to one embodiment;
• 2 B Shows signal waveforms for injection and ejection potentials coming out of parts of the mass spectrometer 1 according to another embodiment;
• 3 Figure 12 shows a schematic block diagram of a control system according to an embodiment;
• 4 Figure 12 shows exemplary mass spectra for ionic species with a low mass-to-charge ratio range, using (a) an existing approach and (b) employing an embodiment;
• 5 Figure 12 shows first exemplary mass spectra for ionic species with a high mass-to-charge ratio range, using (a) an existing approach and (b) an embodiment according to a first approach;
• 6 Figure 12 shows second exemplary mass spectra for ionic species with a high mass-to-charge ratio range, using (a) an existing approach and (b) an embodiment according to a second approach.

Detailed description of a preferred embodiment

The following discussion refers to the well-known in 1 illustrated mass spectrometer. Nevertheless, it should be understood that the techniques described here apply to a wide range of other mass spectrometers, involving other types of mass analyzers and other ways of injecting ions into the mas operate the senanalyzer. The approaches described herein apply in particular to electrostatic traps with upstream ion storage, such that injection from the ion storage device to the electrostatic trap involves ejection from the ion storage device. The invention may be applied in embodiments where there is a difference in the time of arrival of the ions at the electrostatic trap after ejection from the ion storage device which is dependent on the m/z of the ions. The invention may additionally (or alternatively) find application in embodiments where there is an induction (settling) period associated with the one or more injection potentials.

It has been found that the conventional parameters of ion ejection from the C-trap 50 to the orbital trap mass analyzer 70 can result in the loss of low mass-to-charge (m/z) and/or high m/z ratio ions. This can happen for a variety of reasons, as explained below.

One reason why ions with a high m/z ratio can be lost is as follows: By modeling, the flight times of ions with a given m/z ratio from the C-trap 50 to the entrance aperture of the orbital trap mass analyzer 70 could be determined . As mentioned above, ions are ejected from the C-trap 50 by reducing the RF potential applied to its rod electrodes and applying an extraction voltage pulse (typically push-and-pull voltages applied to the corresponding electrodes of the C- Trap 50 can be created). Modeling showed that after such an ejection (a flushing event) ions with a higher m/z ratio, such as e.g. B. those with an m / z ratio of 8000 or more, arrive within about 15 microseconds at the entrance of the electrostatic trap.

The dynamic center electrode (CE) injection waveforms, which traditionally start simultaneously with the ejection potentials for the C-trap ejection event, result in a reduced potential at the CE 72, and thus a reduced field strength for the CE 72 is injected at the CE 72 ion trapping applied (at the same time an increasing dynamic potential is applied to the deflector electrode 65). For positive ions, increasing deflector voltage over time can direct ions into the injection slot, and a lower voltage (more negative voltage) is applied to the CE 72 to reduce the orbital radius of the ions during injection. The increasing voltage on the deflector can compensate for the effect of the negative field "sagging" into the deflector region, so that the deflection field at the injection point remains almost constant and independent of the time-varying negative potential applied to the CE 72. The decreasing field strength means that the high m/z ions arriving in the electrostatic trap after the low m/z ions are exposed to a field from the potential at the CE 72 that is already significantly reduced has amplitude. Therefore, the residual dynamic field that can be used to trap these higher m/z ions is reduced. Therefore, the efficiency of these ions is reduced since a dynamic field is required for ion trapping in the electrostatic trap.

In an orbital trap type electrostatic trap of the kind as in 1 shown, the CE injection waveforms are generated using coupling resistances R _CE = 1 MΩ for the CE 72 and R _DEFL = 2.5 MΩ for the deflector electrode 65; and the intrinsic capacitances from CE 72 and deflector electrode 65 to ground of C _CE ≈ 10 pF and C _DEFL ≈ 5 pF, respectively. Consequently, the time constants of the exponentially varying electric fields (resulting from the CE injection waveforms) R _CE C _CE and R _DEFL C _DEFL are about 10 µs and about 12.5 µs, respectively. Given these time constants, the initial amplitude of the varying field is reduced by a factor of five and only 20% of the remaining dynamic field could be available for trapping these higher m/z ratio species by the time these ions enter the region between the outer detection electrodes 75 and the CE 72 occur. As the CE injection waveforms and resultant fields decrease in magnitude exponentially, the capture efficiency continues to decrease in proportion to the rate of change of voltage (or field strength) over time.

An explanation of why ions with a low m/z ratio can be lost will now be considered: The rapidly changing injection waveforms applied to the CE 72 may have a settling time. This may be about 1 µs for the CE 72 in a recent design of the orbital trap mass analyzer 70, depending on the electronics used to apply this waveform. Such a long settling time can mean that low m/z ions (less than or equal to 100 Th) experience little, if any, dynamic trapping field. These ions would then escape the electrostatic trap in an injection event.

Therefore, it was found that the loss of ions with both low and high m/z ratio is based principally on the time discrepancy between the arrival of ions in the electrostatic trap ejected from the upstream ion storage device (due to a change in the field that traps the ions in this storage device), e.g. B. C-Trap 50, and the dynamic trapping field generated by one or more electrodes connected to the electrostatic trap, such. B. the deflection field and / or injection field is generated based. The timing discrepancy arises from the existing approach, which starts with applying the potentials to start these ejection and capture fields simultaneously. Adjusting the time at which these fields are changed or applied can affect the ability to trap ions with a specific m/z ratio range within the electrostatic trap.

Generally speaking, a method of injecting ions into an electrostatic trap can be considered, comprising: applying an ejection potential to an ion storage device to cause ejection of the ions stored in the ion storage device to the electrostatic trap; and applying one or more injection potentials to one or more electrodes to cause the electrostatic trap to capture ions ejected from the ion storage device. Then the steps of applying the ejection potential and applying the one or more injection potentials are advantageously started at the respective different times. The times are suitably chosen according to the desired values for mass/charge ratios of the ions to be trapped by the electrostatic trap.

In other words, the difference between the time at which the step of applying the ejection potential is started and the time at which the step of applying the one or more injection potentials is started is preferably controlled. Specifically, the magnitude, direction, or both of this difference can be selected according to the desired range of mass to charge ratios of the ions to be trapped by the electrostatic trap. The difference (effectively a delay) can be programmed based on the desired m/z range, which can be user defined and provided as an input.

This general approach can be implemented as a computer program or programmable or programmed logic configured to perform a method described herein when executed by a processor. The computer program can be stored on a computer-readable medium. Also contemplated can be: a mass spectrometer comprising: an ion storage device configured to receive ions for analysis (e.g., when a receiving potential is applied to the device), store the received ions (e.g. when a storage potential is applied to the device) and ejecting the stored ions (e.g., when an ejection potential as described above is applied to the device); an electrostatic trap arranged to receive the ions ejected from the ion storage device; and a controller configured to apply potentials to parts of the mass spectrometer. The electrostatic trap is of the orbital type as described in this document. The controller may be configured to function according to the steps of any of the methods described herein (alone or in combination). It may include structural features (one or more of the following: one or more inputs, one or more outputs, one or more processors, and circuitry) configured to perform one or more of the steps of these methods. The controller may include a computer or processor for executing a computer program or programmable or programmed logic configured to perform any of the methods described herein. The controller may include trigger circuitry to start the ejection potential and one or more injection potentials. The controller may include a programmable delay generator and/or clock to implement a time difference between the respective start times for applying the ejection potential to the ion storage device and applying the one or more injection potentials to the electrodes of the electrostatic trap. Information regarding the values of the mass/charge ratios of the ions to be trapped by the electrostatic trap can be entered into the controller. Such input information can be used with the programmable delay generator and/or clock to implement the time difference between the start times of the potentials.

The details for selecting delays for ion injection are now discussed in more detail. Referring now to 2a signal waveforms are shown for injection and ejection potentials applied to parts of the mass spectrometer 1 according to one embodiment. These waveforms are intended to illustrate the principle of "delayed" ion injection into the orbital trap mass analyzer 70. The rising edge of a pre-trigger signal 101 triggers a reduction in the voltage waveform 105 applied to the CE 72 to a starting voltage of about 3.7 kV. This occurs prior to applying a CLT pulse trigger signal 102 to the CLT 50 to start a voltage pulse 103 applied to the CLT (ie an ejection potential applied to the CLT 50 to eject ions from the CLT 50). Next, the rising edge of an injection pulser trigger signal 104 during ion injection further decreases the CE injection waveform 105 to -5kV (from -3.7kV). A deflector waveform 106 is applied to the deflector electrode 65 synchronously with the CE injection waveform 105 . Note that the deflector injection waveform 106 is a positive pulse which serves to mitigate the field sag effect in the injection slot due to the negative pulse applied to the CE 72 during injection.

As can be seen from the figure, the injection waveform 105 applied to the CE 72 and an injection waveform 106 applied to the deflector electrode 65, both started by the injection pulse trigger signal 104, are shifted in time by an injection delay time 110 to a synchronization pulse 102 which initiates the application of the ejection potential 103 to the C-trap 50 triggers. The waveforms are shown repetitively as multiple spectra are typically acquired with each individual trial. The waveforms on the left and right of the drawing correspond to two different spectra taken with the same delay time 110 between CLT trigger 102 and CE trigger 104. The term "delayed" in this context refers to the shift in time as the CE injection waveform 105 and the deflector injection waveform 106 may start after the CLT ejection pulse 103 or vice versa. Waveforms 105 and 106 may be collectively referred to herein as injection waveforms. When the injection waveforms 105, 106 start after the CLT ejection pulse 103, this is referred to as a positive delay.

If the injection waveforms start before the CLT ejection pulse 103, this is referred to as a negative delay. Referring next to 2 B Figure 12 shows signal waveforms for injection potentials applied to the mass spectrometer prior to ejection potentials according to another embodiment 1 be created. As far as the waveforms go 2 B are the same as those in 2a , the same reference numbers are used. For this embodiment, the injection delay period 120 is negative since the CE trigger waveform 114 precedes the CLT trigger pulse 102 . Consequently, the CE injection waveform 115 and the deflector injection waveform 116 start before the CLT ejection pulse 103. The magnitude of the in 2 B shown negative injection delay period 120 is less than the size of the in 2a shown positive injection delay period 110.

It should be noted that the distance (and hence the time-of-flight, TOF, separation) between the deflector electrode 65 and the CE 72 is significantly smaller than the distance (and therefore the TOF separation) between the CLT 50 and the Deflector electrode 65. In view of this, it is easiest to trigger the deflector injection waveforms 106, 116 and the CE injection waveform 105, 115 simultaneously, although in alternative approaches some shifting between these two signals can be envisaged. So e.g. B. start the CE injection waveform 105,115 shortly after the deflector injection waveform 106,116.

Therefore, a controller is used to appropriately manage and synchronize the signal clock. Referring next to 3 Illustrated is a schematic block diagram of a controller according to one embodiment. This includes a Field Gate Programmable Array (FPGA) controller 200 that provides outputs for a CLT RF board 240 that applies potentials to the CLT 250; and a CE pulser board 220 that supplies the center electrode and the deflector 230 with potentials. The CLT 250 according to this drawing is equivalent to the CLT 50 1 and the center electrode and deflector 230 off 3 are equivalent to the CE 72 and deflector electrode 65 1 . The FPGA controller 200 uses a high precision clock to generate a CLT trigger 205 and a delayed CE inject trigger 210 on different channels. The delay of the CE inject trigger 210 is programmable on the controller 200. The CLT Trigger 205 handles the logic on the CLT RF Board 240 and is synchronous with the ion ejection from the CLT 250, while the CE Inject Trigger 210 starts the injection waveforms applied to the center electrode and deflector 230 and for ion injection into the electrostatic ion trap.

In this way, the synchronization of the CLT trigger signal 102 and the injection waveforms 105 and/or 106 is achieved by means of the FPGA controller 200's integrated high-precision clock. The timing of the waveforms relative to each other can allow ion injection into the electrostatic field region to be triggered so that the CE injection waveform 105 has the optimal level and rate of change of field strength in the electrostatic trap for ions of the desired mass-to-charge ratio is high. Given the above considerations regarding the reasons for the loss of injected ions, the magnitude and/or direction of the delay (or temporal shift) can be selected based on the range of m/z ratios for the ions to be trapped. For ions with low m/z ratios (no more or less than 100 Th), the CE injection waveform 105 (and the deflector injection waveform 106) is approximately 3 µs before the RF waveform applied to the CLT 50 is turned off and applied of the extraction voltage (ion scavenging) counted in periods of the RF waveform applied to the CLT 50. Typically, the RF applied to the CLT 50 has a frequency of 3MHz, so counting 10 RF periods gives a delay of 3 µs. As noted above, this delay is referred to as "negative" because the CE injection potential 105 is applied before the CLT ejection pulse 103 . This time shift is related to the settling time for the injection waveform applied to the CE 72, as discussed above.

For ions with higher m/z ratios (at least or greater than 8000 Th), the CE injection waveform 105 (and the deflector injection waveform 106) will start approximately 20 µs after the RF (ion purge) waveform applied to the CLT 50 is turned off. enabled, and this delay is referred to as "positive". The RF applied to the CLT 50 is turned off at the latest by the time waveforms 105 and 106 are applied, so the positive delay is implemented by a delay generator on the FPGA controller 200. The magnitude of the time shift is related to the time-of-flight of the ions with these m/z ratios from the CLT 50 to entering the electrostatic trap 70 and the time constants of the exponentially varying potentials (or generated electric fields) at the deflector electrode 65 and/or CE 72.

Phase correction of ion signals injected into the orbital trap mass analyzer 70 can be achieved to enable improved Fourier transform and more sophisticated signal processing approaches as described in "Enhanced Fourier transform for Orbitrap mass spectrometry", Lange et al, International Journal of Mass Spectrometry , Vol. 377, 1 February 2015, pages 338-344.

With reference to the general terms set forth above, one approach to consider is when the desired mass-to-charge ratio ranges of ions to be trapped by the electrostatic trap cover a range below (or not above) a threshold mass-to-charge ratio. In this case, the times are selected so that the step of applying the one or more injection potentials occurs before the step of applying the ejection potential. Preferably the mass to charge ratio is 100 Th, although e.g. 70, 75, 80, 90, 110, 120, 130, 140 or 150.

Another approach, which may additionally (or alternatively) be considered, is when the desired mass/charge ratios of the ions to be trapped by the electrostatic trap cover a range above a limit mass/charge ratio. Then the times can be chosen so that the step of applying the ejection potential occurs before the step of applying the one or more injection potentials. The limiting mass/charge ratio is preferably 8000 Th but may e.g. B. also be 7000 Th, 9000 Th or 10000 Th.

The magnitude of the difference between the time at which the step of applying the ejection potential is started (the delay period) and the time at which the step of applying the one or more injection potentials is started is at least 1, 2, 3, 4, 5, 10, 15, 20 or 25 µs. Additionally or alternatively, the size of the difference can be no more than 1, 2, 3, 4, 5, 10, 15, 20 or 25 µs. So e.g. B. applying the one or more injection potentials by at least and/or no more than one of the following values before the step of applying the ejection potential: 1, 2, 3, 4 or 5 µs, e.g. B. a time difference in one of the following ranges: 1 to 5 µs, 1 to 4 µs or 2 to 4 µs. The application of the ejection potential may occur before the step of applying the one or more injection potentials by at least and/or no more than one of the following: 10, 15, 20, or 25 µs.

The magnitude of the difference between the time at which the step of applying the ejection potential is started and the time at which the step of applying the one or more injection potentials is started is advantageously based on one or more of the following list: a time period associated with emission potential; a time period associated with the one or more injection potentials; and a period of time associated with a flight time for ions between the ion storage device and the electrostatic trap. So e.g. B. the time period associated with the one or more injection potentials may be a settling period associated with an electrode to which one of the injection potentials is applied. Then the size of the difference can be at least and/or no more than 1, 2, 3, 4, 5 or 10 times that with the one or more injections potential associated settling period (particularly for ions with a mass-to-charge ratio below the threshold).

Additionally or alternatively, the magnitude of the difference may be based on (at least or more than) one or more of: a discharge time constant associated with the one or more injection potentials; and a time of flight for ions between the ion storage device and the electrostatic trap (particularly for ions with a mass/charge ratio above the limit mass/charge ratio). In particular, the magnitude of the difference may be greater than (or at least) the time of flight for ions between the ion storage device and the electrostatic trap, but less than (or not greater than) the sum of the time of flight for ions between the ion storage device and the electrostatic trap and that with the one or more injection potentials associated discharge time constant. The discharge time constant associated with the one or more injection potentials may depend on at least one resistance and at least one capacitance associated with the electrode to which the one or more injection potentials are applied (eg, the product of resistance and capacitance ). Additionally or alternatively, the discharge time constant can be programmable or adjustable, e.g. B. by means of a digital circuit. The digital circuitry may include Field Programmable Gate Array (FPGA) circuitry. The discharge time constant may be adjustable based on one or more of the following: a user-defined mass/charge range; lower and/or upper mass/charge limits. In this manner, trapping and detection of higher m/z ions (e.g., at least or greater than 8000 Th) in the orbital trap mass analyzer 70 can be accomplished using an injection waveform with a larger discharge time constant.

This aspect (discharge time constant variation) may be used in some embodiments as an alternative to applying the ejection potential and the one or more injection potentials at different times. Thus, in another aspect, the invention features a method of injecting ions into an electrostatic trap, comprising: applying an ejection potential to an ion storage device to cause ions stored in the ion storage device to be ejected to the electrostatic trap; and applying one or more injection potentials to one or more electrodes to cause the electrostatic trap to capture ions ejected from the ion storage device; and wherein a discharge time constant associated with the one or more injection potentials is determined based on desired values of mass-to-charge ratios of ions to be trapped by the electrostatic trap, such as e.g. B. One or more of: user-defined mass-to-charge ratio range; and lower and/or upper mass/charge limit value, can be set.

In this way, the trapping and detection of higher m/z ions (e.g., at least equal to or greater than a first threshold value, e.g., about 8000 Th) in the mass analyzer can be performed using an injection waveform with a relatively larger discharge time constant , compared to trapping and detecting lower m/z ions (e.g., no more or less than a second threshold, e.g., about 100 Th) in the mass analyzer. The capture and detection of such lower m/z ions can be accomplished using an injection waveform with a relatively lower discharge time constant. The first and second thresholds are preferably different (as above), but can also be the same. When the first and second thresholds differ, ions with an m/z between the first and second thresholds can be injected using an injection waveform with the relatively higher discharge time constant, the relatively lower discharge time constant, or a discharge time constant between the relatively higher discharge time constant and the relatively lower discharge time constant ( e.g. approx. 10 µs).

The discharge time constant for an injection waveform applied to one or more trapping electrodes (such as that applied to a center electrode of an orbital trap-type electrostatic trap) is typically the same as the discharge time constant for a deflection electrode ( injection waveform applied to deflect the ions into the trap during the injection process. Alternatively, the discharge time constants can be different. The discharge time constant (or multiple discharge time constants) can have small values such as 5 μs, 10 μs, 15 μs and 25 μs. The discharge time constant (or multiple discharge time constants) must be no greater (or less than) 10 µs, 15 µs and 25 µs or 40 µs. So e.g. For example, for higher m/z ions (greater than or at least equal to the first threshold), the discharge time constant should be around 15 µs, 25 µs or 40 µs (or in a range between any two of these values, e.g. in the range of 15 to 40 µs, or 15 to 25 µs, or 25 to 40 µs, or at least equal to or greater than one of these values, e.g., greater than 15 µs, greater than 25 µs, or greater than 40 µs). Thus, for ions with a lower m/z (smaller or not more than the first threshold) the discharge time constant at about 5 µs or 10 µs (or in a range between these values, i.e. in a range of 5 to 10 µs, or smaller or not larger than these values, e.g. less than 10 µs, or less than 5 µs). Any of the features described herein in relation to this aspect that relate to the discharge time constant may also be combined with any other aspect of this disclosure.

In the preferred embodiment, the electrostatic trap comprises a central electrode and a coaxial outer electrode, e.g. when the electrostatic trap is of the orbital trap type. Then the step of applying one or more injection potentials preferably comprises applying a capture injection potential to the center electrode. In this case of positive ion trapping, the trapping injection potential can be a potential that is dropped from a first (negative) injection potential level to a second, lower (more negative) injection potential level. In the case of negative ion trapping, the trapping injection potential may be a potential that is raised from a first (positive) injection potential level to a second, higher (more positive) injection potential level. Additionally or alternatively, an ion deflector may be provided between the ion storage device and the electrostatic trap. Then the step of applying one or more injection potentials may include applying a deflection injection potential to the ion deflector to cause the ions to move to the electrostatic trap (optionally be focused on an entrance aperture thereof). The step of applying one or more injection potentials preferably includes applying a trapping injection potential to an electrode of the electrostatic trap. When the electrostatic trap is an orbital trap type electrostatic trap, the trapping injection potential can be applied to a central electrode of the electrostatic trap around which the trapped ions orbit. In preferred cases, the deflection injection potential as well as the capture injection potential are applied. Then, the capture injection potential and deflection injection potential application steps are optionally started simultaneously.

The step of applying the ejection potential optionally includes reducing a magnitude - preferably turning off - of a potential applied to one or more electrodes of the ion storage device, such as e.g. B. an RF potential, which serves to store ions in the device, in particular in such a way that the ions stored in the ion storage device are ejected to the electrostatic trap. Preferably, applying the ejection potential simultaneously with reducing or turning off the potential used to store ions in the ion storage device comprises applying an extraction potential (preferably a DC potential) to one or more electrodes of the ion storage device to extract ions from the electrostatic trapping device . The magnitude of the potential applied to the electrode of the ion storage device can be reduced to zero. In the most preferred embodiment, the ion storage device is a curved linear trap.

In some embodiments, the step of applying an ejection potential is initiated by applying an ejection trigger signal to an ejection switch that controls application of the ejection potential. Additionally or alternatively, the step of applying one or more injection potentials is initiated by applying one or more injection trigger signals to at least one injection switch that controls application of the one or more injection potentials. In some embodiments, an RF potential is generated at a predetermined frequency, e.g. B. as a potential to trap ions in the ion storage device. Then the difference between the respective start times of the steps of applying the ejection potential and applying the one or more injection potentials is optionally measured at the predetermined frequency of the RF potential, e.g. B. by counting periods of the HF potential. Since the HF potential represents a high and stable frequency (at least 2 or 3 MHz), periods of at least 1 µs can be measured accurately in this way. Additionally or alternatively, the difference between the respective start times of the steps of applying the ejection potential and applying the one or more injection potentials can be measured by a clock.

The electrostatic trap can preferably be used to perform mass analysis of ions trapped in the electrostatic trap, e.g. B. by image current detection of ion oscillations in the trap (whose frequencies depend on mass/charge ratios of the ions) and signal processing (e.g. Fourier transform) of the detected signal to provide an ion mass spectrum. In embodiments where the electrostatic trap comprises a center electrode and a coaxial outer electrode, such as e.g. in an orbital trap mass analyser, the coaxial outer electrode is preferably divided into at least two parts serving to detect the image current of the oscillating ions, as in the prior art is known, e.g. B. implemented as in Orbitrap mass analyzers (RTM).

The advantages of the approach described will now be illustrated using a few examples. Referring next to 4 exemplary mass spectra for ionic species with a low mass-to-charge ratio range are presented using (a) an existing approach and (b) an embodiment. These mass spectra are intended to demonstrate the efficiency of trapping ions with lower m/z ratios using (a) a standard approach (with no delay between injection waveforms 105 and 106 and the synchronization pulse 102 applied to C-trap 50) and (b) when a negative delay of 3 µs (ie, injection potentials were applied before the ejection potential was applied to the memory device). A mass spectrometer followed for these tests 1 for application. A comparison of these two mass spectra shows that the use of a negative delay between the CLT synchronization pulse 102 and the CE injection waveforms 105 and 106 results in a significantly improved signal-to-noise ratio for the lower mass portion of the spectrum and, in particular, an improvement in the signal -to-noise ratio by a factor of 5 for immonium ions at m/z 74.10.

Referring next to 5 and 6 exemplary mass spectra for ionic species with a high mass-to-charge ratio range are presented using (a) an existing approach and (b) an embodiment. These figures are intended to show the improvement in signal-to-noise ratio for ions with higher m/z ratios that is due to the introduction of a programmable delay between the CLT synchronization pulse 102 and the injection waveforms 105 and 106. These experiments were performed in the native MS mode of a mass spectrometer 1 using the protein complex GroEL (molecular weight 801 kDa), which comprises two non-covalently linked heptameric rings leading to the formation of a 14-complex. This protein complex was further collision-activated in HCD cell 80 to form opposite species 13- and 12-species complexes. A DC bias of 200 V was applied in the area of the HCD cell 80 . In 5 a pressure of 1.4 × 10 ^-4 mbar (1.4 × 10 ^-2 Pa) was used in the C-Trap 50, and in 6 a pressure of 7.7×10 ^-5 mbar (7.7×10 ^-3 Pa) was used in the C-Trap 50. In 5 as well as 6 the first mass spectrum (a) was produced using an existing standard approach (with no delay between the injection waveforms 103 and 104 and the synchronization pulse 105 applied to the C-trap 50). In 5 the second mass spectrum (b) was applied using a positive delay of 25 µs between the CLT synchronization pulse 102 and the injection waveforms 105 and 106. In 6 the second mass spectrum (b) was applied using a positive delay of 20 µs between the CLT synchronization pulse 102 and the injection waveforms 105 and 106.

In 5 the distant signal is observed with an m/z ratio of 12K. At m/z ratios of 18K and 34K, state-of-charge envelopes of 13- and 12-counterdirectional complexes were observed, respectively. In 6 the signal for the ejected subunit is detected at an m/z ratio of 2200 with a lower signal-to-noise ratio. At m/z ratios of 18K and 34K, respectively, state-of-charge envelopes of 13- and 12-counterdirectional complexes were observed. In both cases, the signal-to-noise ratio of the state-of-charge envelopes for the 13-counterbalanced complex is significantly improved, as can be seen from the comparison with the 13-cell signals in the mass spectra in 5 (a) or. 6(a) emerges. Furthermore, in the “delayed” approach, the state-of-charge envelope signals of the 12-counterdirectional complex were acquired with a signal-to-noise ratio of over 50. This can again in 5(b) and 6(b) to be observed. These high m/z species could not be detected under standard conditions as shown in FIG 5(a) and 6(a) evident.

From the foregoing description, it can be seen that the invention enables the highly efficient detection of low m/z (e.g. less than or not more than 100 Th or 80 Th) as well as higher m/z (e.g. at least equal to or greater than 8,000, 12,000, 16,000, or 20,000 Th) using an electrostatic trap. Thus, an electrostatic trap such. an Orbitrap (RTM) mass analyzer, can be used efficiently for mass spectrometry of small molecules and large macromolecular building blocks. Higher detection signal-to-noise ratios can be achieved than with prior art methods. Ion injection can be tuned and optimized for the mass range of ions to be captured and/or analyzed. So e.g. B. A programmable delay between the start of the ejection potential applied to the ion storage device and the one or more injection potentials applied to the electrostatic trap may be used, which may respond to a user-defined m/z range. The highest and lowest m/z ratio within a spectrum can be in the range of 40:1.

Although a specific embodiment has been described, those skilled in the art will recognize that various modifications and changes are possible. In particular, different configurations of mass spectrometers with different types of electrostatic traps and/or ion storage devices can be used. The threshold or limit for detecting a low or high m/z range may differ depending on the types of electrostatic trap and/or ion storage device. Also, the specific signals used to perform ejection from and/or injection into the ion storage device may differ. The magnitude of the delay between the applied ejection and injection waveforms can vary depending on a number of factors including the values of m/z ratios of ions to be trapped in the electrostatic trap. The electrostatic trap is preferably operated as a mass analyzer, but this is not essential and may additionally or alternatively be used for other purposes.

It will therefore be understood that variants of the above embodiments can be made while still falling within the scope of the invention. Any feature disclosed in the specification may be substituted for alternative features serving the same, equivalent or similar purpose, unless otherwise noted. Thus, unless otherwise noted, each feature disclosed is one example of a generic set of equivalent or similar features.

As used in this document, including the claims, singular forms of terms used in this document shall be construed to include the plural form and vice versa, unless the context otherwise indicates. For example, herein, including the claims, unless the context dictates otherwise, a singular reference such as "a" or "an" (such as an analog-to-digital converter) means "one or more" (e.g., one or several analog-to-digital converters). Throughout the specification and claims of this disclosure, the words "comprise," "include," "have," and "include" and variants thereof, for example, "comprising" and "comprises" or the like mean "including without limitation" and is not intended to exclude (and does not exclude) other components.

The use of any and all examples provided herein or phrases referring to examples (“for example”, “such as”, “for example”, and such phrases) is intended only to better illustrate the invention and is not intended to limit the scope of the invention, unless otherwise other is claimed. In no way should any language in the specification be construed as referring to a non-claimed element as essential to the practice of the invention.

All steps described in this specification can be performed in any order or simultaneously, unless otherwise noted or the context dictates otherwise.

All of the features disclosed in this specification may be combined in any combination, except for combinations where at least some of those features and/or steps are mutually exclusive. In particular, the preferred features of the invention apply to all aspects of the invention and can be used in any combination. Likewise, features described in non-essential combinations may be used separately (not combined with each other).

1. 1. Verfahren zum Injizieren von Ionen in eine elektrostatische Orbitalfalle, umfassend:
   • Anlegen eines Ausstoßpotenzials an eine lonenspeichervorrichtung, um das Ausstoßen von in der lonenspeichervorrichtung gespeicherten Ionen in Richtung der elektrostatischen Falle zu veranlassen, und
   • Anlegen von synchronen Injektionspotenzialen an eine mittlere Elektrode der elektrostatischen Falle vom Orbitaltyp und eine mit der elektrostatischen Falle vom Orbitaltyp verbundene Deflektorelektrode, um das Einfangen der aus der lonenspeichervorrichtung ausgestoßenen Ionen durch die elektrostatische Falle zu veranlassen, so dass diese um die mittlere Elektrode kreisen; und
   • wobei die Schritte des Anlegens des Ausstoßpotenzials und des Anlegens des synchronen Injektionspotenzials jeweils zu unterschiedlichen Zeiten beginnen, wobei der Unterschied zwischen den ausgewählten Zeiten auf gewünschten Werten von Masse-/Ladungsverhältnissen von durch die elektrostatische Falle vom Orbitaltyp einzufangenden Ionen basiert.
2. 2. Verfahren nach Ausführungsform 1, wobei eine oder beide einer Größe und einer Richtung der Differenz zwischen der Zeit, zu der der Schritt des Anlegens des Ausstoßpotenzials gestartet wird, und der Zeit, zu der der Schritt des Anlegens des synchronen Injektionspotenzials gestartet wird, basierend auf den gewünschten Werten der Masse-/Ladungsverhältnisse der durch die elektrostatische Falle vom Orbitaltyp einzufangenden Ionen basiert.
3. 3. Verfahren nach Ausführungsform 1 oder Ausführungsform 2, wobei die gewünschten Werte für die Masse-/Ladungsverhältnisse der durch die elektrostatische Falle vom Orbitaltyp einzufangenden Ionen Werte umfasst, die ein Schwellen-Masse-/Ladungsverhältnis unterschreiten, wobei die Differenz der auszuwählenden Zeiten so gestaltet ist, dass der Start des Schritts des Anlegens des einen oder der mehreren Injektionspotenziale vor dem Start des Schritts des Anlegens des Ausstoßpotenzials stattfindet.
4. 4. Verfahren nach Ausführungsform 3, wobei das Schwellen-Masse-/Ladungsverhältnis 100 Thomson beträgt.
5. 5. Verfahren nach Ausführungsform 1 oder Ausführungsform 2, wobei die gewünschten Werte für die Masse-/Ladungsverhältnisse der durch die elektrostatische Falle einzufangenden Ionen Werte umfasst, die ein Grenz-Masse-/Ladungsverhältnis überschreiten, wobei die Differenz der auszuwählenden Zeiten so gestaltet ist, dass der Start des Schritts des Anlegens des Ausstoßpotenzials vor dem Start des Schritts des Anlegens des einen oder der mehreren Injektionspotenziale stattfindet.
6. 6. Verfahren nach Ausführungsform 5, wobei das Grenz-Masse-/Ladungsverhältnis 8000 Thomson beträgt.
7. 7. Verfahren nach einer der vorstehenden Ausführungsformen, wobei die Größe der Differenz zwischen der Zeit, zu der der Schritt des Anlegens des Ausstoßpotenzials beginnt, und der Zeit, zu der der Schritt des Anlegens der einen oder mehreren Injektionspotenziale beginnt, einem der folgenden Werte entspricht: mindestens 3 µs; mindestens 10 µs; mindestens 15 µs; mindestens 20 µs und mindestens 25 µs.
8. 8. Verfahren nach einer der vorstehenden Ausführungsformen, wobei die Größe der Differenz zwischen der Zeit, zu der der Schritt des Anlegens des Ausstoßpotenzials gestartet wird, und der Zeit, zu dem der Schritt des Anlegens des einen oder der mehreren Injektionspotenziale gestartet wird, auf einem oder mehreren Elementen der folgenden Liste basiert: einem mit dem Ausstoßpotenzial verbundenen Zeitraum; einem mit dem einen oder den mehreren Injektionspotenzialen verbundenen Zeitraum; und einem mit einer Flugzeit für Ionen zwischen der lonenspeichervorrichtung und der elektrostatischen Falle verbundenen Zeitraum.
9. 9. Verfahren nach Ausführungsform 8, wobei die Größe der Differenz mindestens das Dreifache eines Einschwingzeitraums in Verbindung mit den synchronen Injektionspotenzialen beträgt.
10. 10. Verfahren nach Ausführungsform 8, wobei die Größe der Differenz basiert auf: einer Entladezeitkonstanten in Verbindung mit den synchronen Injektionspotenzialen, und/oder einer Flugzeit für Ionen zwischen der lonenspeichervorrichtung und der elektrostatischen Falle vom Orbitaltyp.
11. 11. Verfahren nach Ausführungsform 10, wobei die Größe der Differenz größer ist als die Flugzeit für Ionen zwischen der lonenspeichervorrichtung und der elektrostatischen Falle vom Orbitaltyp, aber kleiner als die Summe der Flugzeit für Ionen zwischen der lonenspeichervorrichtung und der elektrostatischen Falle vom Orbitaltyp und der mit dem einen oder den mehreren synchronen Injektionspotenzialen verbundenen Entladezeitkonstanten.
12. 12. Verfahren nach Ausführungsform 10 oder Ausführungsform 11, wobei die mit den synchronen Injektionspotenzialen verbundene Entladezeitkonstante von mindestens einem entsprechenden Widerstand und mindestens einer entsprechenden Kapazität in Verbindung mit der mittleren Elektrode sowie der Deflektorelektrode, an die die synchronen Injektionspotenziale angelegt werden, abhängig ist.
13. 13. Verfahren nach Ausführungsform 10 oder 11, wobei die mit den synchronen Injektionswellenformen verbundene Entladezeitkonstante mittels digitaler Schaltungen programmierbar oder einstellbar ist.
14. 14. Verfahren nach einer der vorstehenden Ausführungsformen, wobei die elektrostatische Falle vom Orbitaltyp die mittlere Elektrode und eine koaxiale äußere Elektrode umfasst und wobei der Schritt des Anlegens von synchronen Injektionspotenzialen das Anlegen eines Einfang-Injektionspotenzials an die mittlere Elektrode umfasst.
15. 15. Verfahren nach Ausführungsform 14, wobei das Einfang-Injektionspotenzial ein Potenzial ist, das von einem ersten Injektionspotenzialniveau auf ein zweites niedrigeres Injektionspotenzialniveau abgesenkt wird.
16. 16. Verfahren nach einer der vorstehenden Ausführungsformen, wobei ein lonendeflektor, der die Deflektorelektrode umfasst, zwischen der lonenspeichervorrichtung und der elektrostatischen Falle vom Orbitaltyp vorgesehen ist, und wobei der Schritt des Anlegens von synchronen Injektionspotenzialen umfasst: Anlegen eines Deflektionsinjektionspotenzials an den lonendeflektor, um die Bewegung der Ionen zur elektrostatischen Falle vom Orbitaltyp zu veranlassen.
17. 17. Verfahren nach einer der vorstehenden Ausführungsformen, wobei der Schritt des Anlegens des Ausstoßpotenzials das Verringern einer Größe eines an eine oder mehrere Elektroden der lonenspeichervorrichtung angelegten Potenzials umfasst, so dass die in der lonenspeichervorrichtung gespeicherten Ionen zur elektrostatischen Falle vom Orbitaltyp ausgestoßen werden.
18. 18. Verfahren nach Ausführungsform 17, wobei der Schritt des Anlegens des Ausstoßpotenzials das Ausschalten des an eine oder mehrere Elektroden der lonenspeichervorrichtung angelegten HF-Potenzials umfasst, und das Anlegen eines DC-Extraktionspotenzials an eine oder mehrere Elektroden der lonenspeichervorrichtung, so dass die in der lonenspeichervorrichtung gespeicherten Ionen zur elektrostatischen Falle vom Orbitaltyp ausgestoßen werden.
19. 19. Verfahren nach einer der vorstehenden Ausführungsformen, wobei die lonenspeichervorrichtung eine gekrümmte lineare Falle ist.
20. 20. Verfahren nach einer der vorstehenden Ausführungsformen, wobei der Schritt des Anlegens eines Ausstoßpotenzials durch Anlegen eines Ausstoß-Auslösesignals an einen Ausstoßschalter, der das Anlegen des Ausstoßpotenzials steuert, beginnt, und/oder wobei der Schritt des Anlegens von synchronen Injektionspotenzialen durch Anlegen von einem oder mehreren Injektions-Auslösesignalen an mindestens einen Injektionsschalter, der das Anlegen der synchronen Injektionspotenziale steuert, beginnt.
21. 21. Verfahren nach einer der vorstehenden Ausführungsformen, wobei ein HF-Potenzial mit einer vorgegebenen Frequenz erzeugt wird und die Differenz zwischen jeweiligen Startzeiten der Schritte des Anlegens des Ausstoßpotenzials und des Anlegens der synchronen Injektionspotenziale mittels der vorgegebenen Frequenz des HF-Potenzials gemessen wird.
22. 22. Computerprogramm, das dazu konfiguriert ist, das Verfahren nach dem vorstehenden Ausführungsform bei Betrieb mit einem Prozessor auszuführen.
23. 23. Massenspektrometer, umfassend:
    • eine lonenspeichervorrichtung, die dazu konfiguriert ist, Ionen zur Analyse zu empfangen, die empfangenen Ionen zu speichern und die gespeicherten Ionen auszustoßen;
    • eine elektrostatische Falle vom Orbitaltyp mit einer mittleren Elektrode und einer dazugehörigen Deflektorelektrode, die dazu angeordnet ist, die aus der lonenspeichervorrichtung ausgestoßenen Ionen zu empfangen; und
    • einen Controller, der dazu konfiguriert ist, Potenziale an das Massenspektrometer entsprechend dem Verfahren nach einer der Ausführungsformen 1 bis 21 anzulegen.

The present technology can also be defined by the following numbered embodiments.

1. Claims 1. A method of injecting ions into an electrostatic orbital trap, comprising:
   • applying an ejection potential to an ion storage device to cause ions stored in the ion storage device to be ejected towards the electrostatic trap, and
   • applying synchronous injection potentials to a center electrode of the orbital-type electrostatic trap and a deflector electrode connected to the orbital-type electrostatic trap to cause the ions ejected from the ion storage device to be captured by the electrostatic trap to orbit around the center electrode; and
   • wherein the steps of applying the ejection potential and applying the synchronous injection potential each begin at different times, the difference between the selected times being based on desired values of mass-to-charge ratios of ions to be trapped by the orbital-type electrostatic trap.
2. 2. The method of embodiment 1, wherein either or both of a magnitude and a direction of the difference between the time at which the ejection potential application step is started and the time at which the synchronous injection potential application step is started is based is based on the desired values of the mass/charge ratios of the ions to be trapped by the orbital-type electrostatic trap.
3. 3. The method according to embodiment 1 or embodiment 2, wherein the desired values for the mass/charge ratios of the ions to be trapped by the orbital-type electrostatic trap comprise values falling below a threshold mass/charge ratio, the difference in the times to be selected being such is that the start of the step of applying the one or more injection potentials occurs before the start of the step of applying the ejection potential.
4. 4. The method of embodiment 3, wherein the threshold mass-to-charge ratio is 100 Thomson.
5. 5. The method according to embodiment 1 or embodiment 2, wherein the desired values for the mass/charge ratios of the ions to be trapped by the electrostatic trap comprise values exceeding a limit mass/charge ratio, the difference in times to be selected being such that that the start of the step of applying the ejection potential occurs before the start of the step of applying the one or more injection potentials.
6. 6. The method of embodiment 5, wherein the limit mass-to-charge ratio is 8000 Thomson.
7. 7. The method of any preceding embodiment, wherein the magnitude of the difference between the time the step of applying the ejection potential begins and the time the step of applying the one or more injection potentials begins is one of the following : at least 3 µs; at least 10 µs; at least 15 µs; at least 20 µs and at least 25 µs.
8. 8. The method of any preceding embodiment, wherein the magnitude of the difference between the time at which the step of applying the ejection potential is started and the time at which the step of applying the one or more injection potentials is started is a or more of the following list: a time period associated with the emission potential; a time period associated with the one or more injection potentials; and a period of time associated with a flight time for ions between the ion storage device and the electrostatic trap.
9. 9. The method of embodiment 8, wherein the magnitude of the difference is at least three times a transient period associated with the synchronous injection potentials.
10. 10. The method of embodiment 8, wherein the magnitude of the difference is based on: a discharge time constant associated with the synchronous injection potentials, and/or a time of flight for ions between the ion storage device and the orbital-type electrostatic trap.
11. 11. The method of embodiment 10, wherein the magnitude of the difference is greater than the flight time for ions between the ion storage device and the orbital-type electrostatic trap, but smaller than the sum of the flight time for ions between the ion storage device and the orbital-type electrostatic trap and the with the discharge time constant associated with the one or more synchronous injection potentials.
12. 12. The method of embodiment 10 or embodiment 11, wherein the discharge time constant associated with the synchronous injection potentials is dependent on at least one corresponding resistance and at least one corresponding capacitance associated with the center electrode and the deflector electrode to which the synchronous injection potentials are applied.
13. 13. The method of embodiment 10 or 11, wherein the discharge time constant associated with the synchronous injection waveforms is programmable or adjustable using digital circuitry.
14. 14. The method of any preceding embodiment, wherein the orbital-type electrostatic trap comprises the central electrode and a coaxial outer electrode, and wherein the step of applying synchronous injection potentials comprises applying a trapping injection potential to the central electrode.
15. 15. The method of embodiment 14, wherein the capture injection potential is a potential that is dropped from a first injection potential level to a second, lower injection potential level.
16. 16. The method according to any one of the preceding embodiments, wherein an ion deflector comprising the deflector electrode between the ion storage device and the orbital-type electrostatic trap, and wherein the step of applying synchronous injection potentials comprises: applying a deflection injection potential to the ion deflector to cause the ions to move to the orbital-type electrostatic trap.
17. 17. The method of any preceding embodiment, wherein the step of applying the ejection potential comprises decreasing a magnitude of a potential applied to one or more electrodes of the ion storage device such that the ions stored in the ion storage device are ejected to the orbital-type electrostatic trap.
18. 18. The method of embodiment 17, wherein the step of applying the ejection potential comprises turning off the RF potential applied to one or more electrodes of the ion storage device, and applying a DC extraction potential to one or more electrodes of the ion storage device such that the in the Ions stored in the ion storage device are ejected to the orbital-type electrostatic trap.
19. 19. The method of any preceding embodiment, wherein the ion storage device is a curved linear trap.
20. 20. The method of any preceding embodiment, wherein the step of applying an ejection potential begins by applying an ejection trigger signal to an ejection switch that controls application of the ejection potential, and/or wherein the step of applying synchronous injection potentials begins by applying a or multiple injection trigger signals to at least one injection switch that controls application of the synchronous injection potentials.
21. 21. The method according to any one of the preceding embodiments, wherein an HF potential is generated with a predetermined frequency and the difference between respective start times of the steps of applying the ejection potential and applying the synchronous injection potentials is measured using the predetermined frequency of the HF potential.
22. 22. A computer program configured to perform the method of the above embodiment when operating on a processor.
23. 23. A mass spectrometer comprising:
    • an ion storage device configured to receive ions for analysis, store the received ions, and eject the stored ions;
    • an orbital-type electrostatic trap having a central electrode and an associated deflector electrode arranged to receive ions ejected from the ion storage device; and
    • a controller configured to apply potentials to the mass spectrometer according to the method of any one of embodiments 1-21.

Claims (26)

A method of injecting ions into an orbital-type electrostatic trap (70), comprising: applying an ejection potential (103) to an ion storage device (50) to cause ions stored in the ion storage device (50) to be ejected toward the orbital-type electrostatic trap (70), and applying one or more injection potentials (105, 106, 115, 116) to an electrode (72) associated with the electrostatic trap (70) to cause the electrostatic trap (70) to trap ions ejected from the ion storage device (50). causing them to revolve around a central electrode (72); and wherein the steps of applying the ejection potential (103) and applying one or more injection potentials (105, 106, 115, 116) each begin at different times, the difference (110, 120) in times being at desired values of mass/charge ratios of ions to be trapped by the electrostatic trap (70), and wherein an RF potential is generated at a predetermined frequency and the difference between respective start times of the steps of applying the ejection potential (103) and applying the one or more injection potentials (105 , 106, 115, 116) is measured using the predetermined frequency of the HF potential. procedure after claim 1 , wherein applying the one or more injection potentials (105, 106, 115, 116) to the electrode associated with the electrostatic trap (70) comprises applying one or more injection potentials (105, 106, 115, 116) to the middle electrode (72 ) the orbital-type electrostatic trap (70), and applying one or more injection potentials (105, 106, 115, 116) to a deflector electrode (65) associated with the orbital-type electrostatic trap (70). procedure after claim 2 wherein the injection potentials (105, 106, 115, 116) are synchronously applied to the center electrode (72) of the orbital-type electrostatic trap (70) and the deflector electrode (65) associated with the orbital-type electrostatic trap (70). procedure after claim 2 or claim 3 wherein an ion deflector comprising the deflector electrode (65) is provided between the ion storage device (50) and the orbital-type electrostatic trap (70), and wherein the step of applying injection potentials (105, 106, 115, 116) comprises applying a deflecting injection potential (105, 106, 115, 116) to the ion deflector to cause the ions to move toward the orbital-type electrostatic trap (70). A method according to any preceding claim, wherein the difference between the respective start times of the steps of applying the ejection potential (103) and applying the one or more injection potentials (105, 106, 115, 116) is measured by counting periods of the RF potential . A method according to any preceding claim, wherein the RF potential has a frequency of at least 2 MHz. A method according to any preceding claim, wherein the RF potential is a potential for confining ions within the ion storage device (50). procedure after claim 1 , wherein the desired values for the mass/charge ratios of the ions to be trapped by the electrostatic trap (70) comprise values falling below a threshold mass/charge ratio, the difference in the times to be selected being such that the start of the step of applying the one or more injection potentials (105, 106, 115, 116) prior to the start of the step of applying the ejection potential (103). procedure after claim 8 , where the threshold mass/charge ratio is 100 Thomson (≈ 1.036426 × 10 ^-6 kg·C ^-1 ). procedure after claim 1 , wherein the desired values for the mass/charge ratios of the ions to be trapped by the electrostatic trap (70) comprise values exceeding a limit mass/charge ratio, the difference in the times to be selected being such that the start of the step of applying the ejection potential (103) occurs prior to the start of the step of applying the one or more injection potentials (105, 106, 115, 116). procedure after claim 10 , where the limiting mass/charge ratio is 8000 Thomson (≈ 8.291408 × 10 ^-5 kg·C ^-1 ). The method of any preceding claim, wherein the magnitude of the difference between the time the step of applying the ejection potential (103) begins and the time the step of applying the one or more injection potentials (105, 106, 115 , 116) starts, corresponds to one of the following values: at least 3 µs; at least 10 µs; at least 15 µs; at least 20 µs and at least 25 µs. The method of any preceding claim, wherein the magnitude of the difference between the time the step of applying the ejection potential (103) is started and the time the step of applying the one or more injection potentials (105, 106 , 115, 116) is started based on one or more of the following list: a time period associated with the ejection potential (103); a time period associated with the one or more injection potentials (105, 106, 115, 116); and a period of time associated with a flight time for ions between the ion storage device (50) and the electrostatic trap (70). procedure after Claim 13 , where the magnitude of the difference is at least three times a transient period associated with the injection potentials (105, 106, 115, 116). procedure after Claim 13 , wherein the magnitude of the difference is based on: a discharge time constant associated with the injection potentials (105, 106, 115, 116), and/or a time of flight for ions between the ion storage device (50) and the electrostatic trap (70). procedure after claim 15 , wherein the magnitude of the difference is greater than the time of flight for ions between the ion storage device (50) and the electrostatic trap (70) but less than the sum of the time of flight for ions between the ion storage device (50) and the electrostatic trap (70) and the discharge time constant associated with the one or more injection potentials (105, 106, 115, 116). procedure after claim 15 or Claim 16 , if Claim 13 after claim 2 where the discharge time constant associated with the injection potentials (105, 106, 115, 116) is associated with at least one corresponding resistance and at least one corresponding capacitance Connection with the middle electrode (72) and the deflector electrode (65) to which the injection potentials (105, 106, 115, 116) are applied depends. procedure after claim 15 or 16 , wherein the discharge time constant associated with the injection waveforms is programmable or adjustable using digital circuitry. procedure after claim 1 wherein the orbital-type electrostatic trap (70) comprises the central electrode (72) and a coaxial outer electrode and wherein the step of applying injection potentials (105, 106, 115, 116) comprises applying a trapping injection potential (105, 106, 115, 116) to the central electrode (72). procedure after claim 19 , wherein the capture injection potential (105, 106, 115, 116) is a potential that is dropped from a first injection potential level to a second lower injection potential level. The method of any preceding claim, wherein the step of applying the ejection potential (103) comprises reducing a magnitude of a potential applied to one or more electrodes of the ion storage device (50) such that the ions stored in the ion storage device (50) electrostatically trap (70) are expelled. procedure after Claim 21 , wherein the step of applying the ejection potential (103) comprises turning off the RF potential applied to one or more electrodes of the ion storage device (50), and applying a DC extraction potential to one or more electrodes of the ion storage device (50) such that the ions stored in the ion storage device (50) are ejected to the electrostatic trap (70). A method according to any one of the preceding claims, wherein the ion storage device (50) is a curved linear trap. The method of any preceding claim, wherein the step of applying an ejection potential (103) begins by applying an ejection trigger signal to an ejection switch that controls the application of the ejection potential (103), and/or wherein the step of applying one or multiple injection potentials (105, 106, 115, 116) by applying one or more injection trigger signals to at least one injection switch that controls the application of the injection potentials (105, 106, 115, 116). A computer program configured to perform the method of any preceding claim when operated on a processor. A mass spectrometer comprising: an ion storage device (50) configured to receive ions for analysis, store the received ions and eject the stored ions; an electrostatic trap (70) arranged to receive the ions ejected from the ion storage device (50); and a controller (200) configured to send potentials to the mass spectrometer according to the method of any one of Claims 1 until 24 to create.

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